Search results for "equilibrium"

Preselection statistics and Random Forest classification identify population informative single nucleotide polymorphisms in cosmopolitan and autochth…

2018

Commercial single nucleotide polymorphism (SNP) arrays have been recently developed for several species and can be used to identify informative markers to differentiate breeds or populations for several downstream applications. To identify the most discriminating genetic markers among thousands of genotyped SNPs, a few statistical approaches have been proposed. In this work, we compared several methods of SNPs preselection (Delta, F st and principal component analyses (PCA)) in addition to Random Forest classifications to analyse SNP data from six dairy cattle breeds, including cosmopolitan (Holstein, Brown and Simmental) and autochthonous Italian breeds raised in two different regions and …

Population Structure in the Model Grass Brachypodium distachyon Is Highly Correlated with Flowering Differences across Broad Geographic Areas

2016

The small, annual grass Brachypodium distachyon (L.) Beauv., a close relative of wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.), is a powerful model system for cereals and bioenergy grasses. Genome-wide association studies (GWAS) of natural variation can elucidate the genetic basis of complex traits but have been so far limited in B. distachyon by the lack of large numbers of well-characterized and sufficiently diverse accessions. Here, we report on genotyping-by-sequencing (GBS) of 84 B. distachyon, seven B. hybridum, and three B. stacei accessions with diverse geographic origins including Albania, Armenia, Georgia, Italy, Spain, and Turkey. Over 90,000 high-quality single-nu…

Conservation status and historical relatedness of Italian cattle breeds

2018

Background In the last 50 years, the diversity of cattle breeds has experienced a severe contraction. However, in spite of the growing diffusion of cosmopolite specialized breeds, several local cattle breeds are still farmed in Italy. Genetic characterization of breeds represents an essential step to guide decisions in the management of farm animal genetic resources. The aim of this work was to provide a high-resolution representation of the genome-wide diversity and population structure of Italian local cattle breeds using a medium-density single nucleotide polymorphism (SNP) array. Results After quality control filtering, the dataset included 31,013 SNPs for 800 samples from 32 breeds. Ou…

Double-exponential kinetics of binding and redistribution of the fluorescent dyes in cell membranes witness for the existence of lipid microdomains.

2018

Abstract New technique of detecting lateral heterogeneity of the plasma membrane of living cells by means of membrane-binding fluorescent dyes is proposed. The kinetics of dye incorporation into the membrane or its lateral diffusion inside the membrane is measured and decomposed into exponential components by means of the Maximum Entropy Method. Two distinct exponential components are obtained consistently in all cases for several fluorescent dyes, two different cell lines and in different types of experiments including spectroscopy, flow cytometry and fluorescence recovery after photobleaching. These components are attributed to the liquid-ordered and disordered phases in the plasma membra…

2018

Genome-Wide-Association-Studies have become a powerful method to link point mutations (e.g. single nucleotide polymorphisms (SNPs)) to a certain phenotype or a disease. However, their power to detect SNPs associated to polygenic diseases such as Alzheimer's Disease (AD) is limited, since they can only infer the pairwise relation of single SNPs to the phenotype and ignore possible effects of various SNP combinations. The common method to probe these possible complex genetic patterns is to compute a measure called linkage disequilibrium (LD). Despite the fact that several predictive patterns found with LD could successfully be applied to medical diagnosis, this measure still holds several dra…

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

2017

International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…

Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis

2017

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluat…

A stable brain from unstable components: Emerging concepts and implications for neural computation.

2017

Neuroscientists have often described the adult brain in similar terms to an electronic circuit board- dependent on fixed, precise connectivity. However, with the advent of technologies allowing chronic measurements of neural structure and function, the emerging picture is that neural networks undergo significant remodeling over multiple timescales, even in the absence of experimenter-induced learning or sensory perturbation. Here, we attempt to reconcile the parallel observations that critical brain functions are stably maintained, while synapse- and single-cell properties appear to be reformatted regularly throughout adult life. In this review, we discuss experimental evidence at multiple …

Association study of MMP8 gene in osteoarthritis.

2016

Objectives: Osteoarthritis (OA) is a joint disease common in the elderly. There is a prior functional evidence for different matrix metalloproteinases (MMPs), such as MMP8 and MMP9, having a role in the breakdown of cartilage extracellular matrix in OA. Thus, we analyzed whether the common genetic variants of MMP8 and MMP9 contribute to the risk of OA. Materials and methods: In total, 13 common tagging single-nucleotide polymorphisms (SNPs) were studied in a discovery knee OA cohort of 185 cases and 895 controls. For validation, two knee OA replication cohorts and two hand OA replication cohorts were studied (altogether 1369 OA cases, 4445 controls in the five cohorts). The chi(2) test for …

Direct Visualization of the Conformational Dynamics of Single Influenza Hemagglutinin Trimers

2018

Influenza hemagglutinin (HA) is the canonical type I viral envelope glycoprotein and provides a template for the membrane-fusion mechanisms of numerous viruses. The current model of HA-mediated membrane fusion describes a static "spring-loaded" fusion domain (HA2) at neutral pH. Acidic pH triggers a singular irreversible conformational rearrangement in HA2 that fuses viral and cellular membranes. Here, using single-molecule Förster resonance energy transfer (smFRET)-imaging, we directly visualized pH-triggered conformational changes of HA trimers on the viral surface. Our analyses reveal reversible exchange between the pre-fusion and two intermediate conformations of HA2. Acidification of p…